Estrogen Treatment Reverses Prematurity-Induced Disruption in Cortical Interneuron Population

Development of cortical interneurons continues until the end of human pregnancy. Premature birth deprives the newborns from the supply of maternal estrogen and a secure intrauterine environment. Indeed, preterm infants suffer from neurobehavioral disorders. This can result from both preterm birth and associated postnatal complications, which might disrupt recruitment and maturation of cortical interneurons. We hypothesized that interneuron subtypes, including parvalbumin-positive (PV(+)), somatostatin-positive (SST(+)), calretinin-positive (CalR(+)), and neuropeptide Y-positive (NPY(+)) interneurons, were recruited in the upper and lower cortical layers in a distinct manner with advancing gestational age. In addition, preterm birth would disrupt the heterogeneity of cortical interneurons, which might be reversed by estrogen treatment. These hypotheses were tested by analyzing autopsy samples from premature infants and evaluating the effect of estrogen supplementation in prematurely delivered rabbits. The PV(+) and CalR(+) neurons were abundant, whereas SST(+) and NPY(+) neurons were few in cortical layers of preterm human infants. Premature birth of infants reduced the density of PV(+) or GAD67(+) neurons and increased SST(+) interneurons in the upper cortical layers. Importantly, 17 beta-estradiol treatment in preterm rabbits increased the number of PV(+) neurons in the upper cortical layers relative to controls at postnatal day 14 (P14) and P21 and transiently reduced SST population at P14. Moreover, protein and mRNA levels of Arx, a key regulator of cortical interneuron maturation and migration, were higher in estrogen-treated rabbits relative to controls. Therefore, deficits in PV(+) and excess of SST(+) neurons in premature newborns are ameliorated by estrogen replacement, which can be attributed to elevated Arx levels. Estrogen replacement might enhance neurodevelopmental outcomes in extremely preterm infants.SIGNIFICANCE STATEMENT Premature birth often leads to neurodevelopmental delays and behavioral disorders, which may be ascribed to disturbances in the development and maturation of cortical interneurons. Here, we show that preterm birth in humans is associated with reduced population of parvalbumin-positive (PV(+)) neurons and an excess of somatostatin-expressing interneurons in the cerebral cortex. More importantly, 17 beta-estradiol treatment increased the number of PV(+) neurons in preterm-born rabbits, which appears to be mediated by an elevation in the expression of Arx transcription factor. Hence the present study highlights prematurity-induced reduction in PV(+) neurons in human infants and reversal in their population by estrogen replacement in preterm rabbits. Because preterm birth drops plasma estrogen level 100-fold, estrogen replacement in extremely preterm infants might improve their developmental outcome and minimize neurobehavioral disorders

Changes in the transcriptomic profile of cumulus cells under the influence of cumulus-oocytes complex pre-incubation

Abstract Pre-incubation of the cumulus-oocyte complex (COCs) may lead to better function of cumulus cells (CCs) and higher oocyte quality by changing the transcriptomic profile of CCs. 140 cumulus cell samples were isolated from 12 participants and divided into two groups based on pre-incubation time. In the T0 group, the COCs were immediately dissected to separate the CCs from around the oocytes. In the T2 group, CCs were prepared after 2 h of incubation. Then, the transcriptomic profile of the CCs of the non pre-incubation group was compared to the 2-h pre-incubation group. Confirmation of RNA sequencing results was done via qRT‑PCR. The CCs transcriptome analysis showed 17 genes were downregulated and 22 genes upregulated in the T2 group compared to the T0 group. Also, the pathways related to ATP production (oxidative phosphorylation, electron transport chain, and Mitochondrial complex I assembly model OXPHOS system), TNF-alpha signaling pathway, and glucocorticoid receptor pathway increased in the T2 group compared to the T0 group. Also, the TGF-β pathway was decreased in the T2 group compared to the T0 group. This study showed that 2 h pre-incubation leads to changes in important pathways in CCs, which positively affects oocyte quality

Inpatient diagnoses of idiopathic normal pressure hydrocephalus in the United States: Demographic and socioeconomic disparities

Introduction: Epidemiology provides an avenue for identifying disease pathogenesis, hence determining national incidence, along with socioeconomic and demographic variables involved in iNPH, can provide direction in elucidating the etiology and addressing healthcare inequalities. Methods: To investigate incidence (per 100,000) of iNPH diagnoses applied to the inpatient population, with respect to sex, age, income, residence, and race/ethnicity, we queried the largest American administrative dataset (2008–2016), the National (Nationwide) Inpatient Sample (NIS), which surveys 20% of United States (US) discharges. Results: Annual national inpatient incidence (with 25th and 75th quartiles) for iNPH diagnoses was 2.86 (2.72, 2.93). Males had an inpatient incidence of 3.27 (3.11, 3.39), higher (p = 0.008) than female at 2.45 (2.41, 2.47). Amongst age groups inpatient incidence varied (p = 0.000004) and was largest amongst the 85+ group at 18.81 (16.40, 19.95). Individuals with middle/high income had an inpatient incidence of 2.96 (2.77, 3.06), higher (p = 0.008) than the 2.37 (2.24, 2.53) of low-income patients. Depending on whether patients lived in urban, suburban, or rural communities, inpatient incidence diverged (p = 0.01) as follows, respectively: 2.65; 2.66; 3.036. Amongst race/ethnicity (p = 0.000003), inpatient incidence for Whites, Blacks, Hispanics, Asian/Pacific Islanders, and Native Americans were as follows, respectively: 3.88 (3.69, 3.93), 1.065 (1.015, 1.14); 0.82 (0.76, 0.85); 0.43 (0.33, 0.52); 0.027 (0.026, 0.12). Conclusion: In the US, inpatient incidence for iNPH diagnoses exhibited disparities between socioeconomic and demographic strata, emphasizing a healthcare inequality. Disproportionately, diagnoses were applied most to patients who were White, male, 65 and older, middle/high income, and living in rural communities

The study of serum and tissue cholesterol levels in children undergoing tonsillectomy

Background: Inflammatory and obstructive tonsillar diseases are among the most common diseases in childhood, and tonsillectomy is one of the most common surgical procedures in children. Current evidence indicates the potential association between cholesterol and inflammation. Objective: The aim of this study was to determine the levels of serum and tissue cholesterol in children undergoing tonsillectomy by gas-liquid chromatography. Methods: Eighty six children with an average age of 7.02±0.24 who referred to Tabriz Children's Hospital were studied with signs of infection and large tonsils. Tonsillectomy was performed and tissues were evaluated by using hematoxylin-eosin technique. The sampling process lasted for one year from February 2010 to 2011. Patients were divided in two groups of hyperplasia (n=48) and chronic tonsillitis (n=38). The cholesterol content of serum and tonsillar tissues were extracted and measured by gas-liquid chromatography. Findings: There was no significant difference in serum cholesterol between the two groups (P=0.32). However, the tonsillar cholesterol level in the chronic tonsillitis group was higher than the hyperplasia group (P=0.038). In the chronic tonsillitis group, the level of tissue cholesterol in the pathological grade 4 was significantly higher than other grades (P=0.009). Conclusion: The level of tissue cholesterol in children with chronic tonsillitis was higher than those with tonsillar hyperplasia and this level was higher in tonsillitis with higher pathological grade

Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing

Hydrogel-based bioadhesives have emerged as alternatives for sutureless wound closure, since they can mimic the composition and physicochemical properties of the extracellular matrix. However, they are often associated with poor mechanical properties, low adhesion to native tissues, and lack of antimicrobial properties. Herein, a new sprayable, elastic, and biocompatible composite hydrogel, with broad-spectrum antimicrobial activity, for the treatment of chronic wounds is reported. The composite hydrogels were engineered using two ECM-derived biopolymers, gelatin methacryloyl (GelMA) and methacryloyl-substituted recombinant human tropoelastin (MeTro). MeTro/GelMA composite hydrogel adhesives were formed via visible light-induced crosslinking. Additionally, the antimicrobial peptide Tet213 was conjugated to the hydrogels, instilling antimicrobial activity against Gram (+) and (-) bacteria. The physical properties (e.g. porosity, degradability, swellability, mechanical, and adhesive properties) of the engineered hydrogel could be fine-tuned by varying the ratio of MeTro/GelMA and the final polymer concentration. The hydrogels supported in vitro mammalian cellular growth in both two-dimensional and three dimensional cultures. The subcutaneous implantation of the hydrogels in rats confirmed their biocompatibility and biodegradation in vivo. The engineered MeTro/GelMA-Tet213 hydrogels can be used for sutureless wound closure strategies to prevent infection and promote healing of chronic wounds